| 1. |
- Brundin, Patrik, et al.
(författare)
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Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
- 2000
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Ingår i: Brain. - 1460-2156. ; 123, s. 1380-1390
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Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
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| 2. |
- Hagell, Peter, et al.
(författare)
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Sequential bilateral transplantation in Parkinson's disease: effects of the second graft
- 1999
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156. ; 122:6, s. 1121-1132
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Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.
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| 3. |
- Nikkhah, G, et al.
(författare)
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Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture
- 1993
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Ingår i: Experimental Brain Research. - 0014-4819 .- 1432-1106. ; 92:3, s. 516-523
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Tidskriftsartikel (refereegranskat)abstract
- The effect of two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, was tested on dissociated cell cultures of ventral mesencephalon from rat and human embryos. PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures. The mean number of TH-positive cells in the PDGF-BB-treated rat culture was 64% and 106% higher than in the control cultures after 7 and 10 days in vitro, respectively. Corresponding figures for human TH-positive neurons were 90% and 145%. The influence of PDGF-BB was specific for TH-positive neurons and not a general trophic effect, since no change of either total cell number or metabolic activity was found. In PDGF-BB-treated cultures of human but not rat tissue the TH-positive neurons had longer neurites than observed in control or PDGF-AA-treated cultures. These data indicate that PDGF-BB may act as a trophic factor for mesencephalic dopaminergic neurons and suggest that administration of PDGF-BB could ameliorate degeneration and possibly promote axonal sprouting of these neurons in vivo.
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| 4. |
- Smits, A, et al.
(författare)
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Expression of platelet-derived growth factor in and around intrastriatal embryonic mesencephalic grafts
- 1993
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 2:2, s. 151-162
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Tidskriftsartikel (refereegranskat)abstract
- The expression of platelet-derived growth factor (PDGF) was investigated in the embryonic donor tissue and surrounding host brain before and after intracerebral transplantation in a rat model of Parkinson's disease (PD). Ventral mesencephalic tissue from E13-E15 rat embryos was dissociated and implanted into adult rats with unilateral lesions of the mesostriatal dopamine system. Immunohistochemical studies showed that the majority of the grafted cells were PDGF-positive at early time points after grafting. However, the immunostaining gradually decreased, and had disappeared almost completely 3 wk after transplantation. These results were in agreement with in situ hybridization data demonstrating detectable levels of mRNA for PDGF chains in graft cells after 1, but not after 6 wk. In contrast, a large number of PDGF-immunoreactive cells was observed in the host brain adjacent to the grafts from 1 wk after transplantation, and increasing with time. Increased expression of PDGF was also observed in response to a sham-operation (injection of vehicle), although the number of PDGF-positive cells seemed lower than after grafting of embryonic tissue. Double immunofluorescence labeling of these cells with an anti-glial fibrillary acidic protein (GFAP) antiserum and a monoclonal antibody against PDGF B-chain, indicated that the PDGF-positive cells were astrocytes. The dynamic expression of PDGF in and around intrastriatal embryonic mesencephalic implants has several, potentially important, implications for graft survival and function. Glial cells could utilize the elevated levels of PDGF to proliferate in a reactive gliosis, and PDGF might also augment immune responses. It is also possible that PDGF increases the survival of, and promotes neurite outgrowth from, grafted dopaminergic neurons.
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| 5. |
- Wenning, Gregor K, et al.
(författare)
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Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease
- 1997
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 42:1, s. 95-107
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Tidskriftsartikel (refereegranskat)abstract
- Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.
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